Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Fatty Acids Lipidome and Oxidative Stress in Liver Transplantation

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by University of Roma La Sapienza
Sponsor:
Information provided by (Responsible Party):
Luigi Iuliano, University of Roma La Sapienza
ClinicalTrials.gov Identifier:
NCT01389115
First received: May 6, 2011
Last updated: January 30, 2014
Last verified: January 2014

May 6, 2011
January 30, 2014
July 2001
July 2014   (final data collection date for primary outcome measure)
Post operative graft function after liver transplantation [ Time Frame: Change in graft function after 7 and 30 days after liver transplantation ] [ Designated as safety issue: No ]
• Multiple lipid metabolism biomarkers (fatty acids, cholesterol and oxysterols) are evaluated in the plasma of liver cirrhosis patients before liver transplantation. A logistic regression model is used to evaluate which of these biomarkers is an independent predictor of graft function
Same as current
Complete list of historical versions of study NCT01389115 on ClinicalTrials.gov Archive Site
Early gene expression in the liver graft [ Time Frame: 30 days ] [ Designated as safety issue: No ]
Assessment of lipid metabolism-, oxidative stress-, and ER stress-gene expression in graft tissue liver tissue specimens of patients undergoing organ transplantation and their impact on graft function. Lipid metabolism and ER gene expression (genes: LDL-R, HMGCR, CD81, SREBP2, NPC1L1, XBP-1, XBP2, ATF6, GRP78, GRP94, LXR, INSIG1, INSIG2) in liver graft specimens at transplantation before and after ischemia-reperfusion injury; downregulated and upregulated genes are related to early graft function.
Early gene expression in the liver graft [ Time Frame: 30 days ] [ Designated as safety issue: No ]
Assessment of lipid metabolism-, oxidative stress-, and ER stress-gene expression in graft tissue liver tissue specimens of patients undergoing organ transplantation and their impact on graft function. Lipid metabolism and ER gene expression (LDL-R, HMGCR, CD81, SREBP2, NPC1L1, XBP-1, XBP2, ATF6, GRP78, GRP94, LXR, INSIG1, INSIG2 in liver graft specimens at transplantation before and after ischemia-reperfusion injury; downregulated and upregulated genes are related to early graft function.
Not Provided
Not Provided
 
Fatty Acids Lipidome and Oxidative Stress in Liver Transplantation
Fatty Acids Lipidome and Oxidative Stress Markers as Indicators of Liver Transplant Outcome

The purpose of this study is to determine lipid metabolism in chronic liver disease in the attempt to find a useful biomarker of liver function and of prognostic value of graft function in those patients who undergo liver transplant. The present study enrolls subjects with liver cirrhosis (with different ethiology), including subjects eligible for a full-size liver transplantation, and healthy controls.

Liver has a central role in fatty acids metabolism that is impaired in chronic liver diseases. Polyunsaturated fatty acids are reportedly reduced in liver cirrhosis, which is considered a condition of essential fatty acids deficiency. However, there is a paucity of data concerning the level of the multitude of circulating fatty acids in liver cirrhosis. Oxidative stress is involved in the pathogenesis of chronic liver disease and fibrosis. Increased oxidative stress with impaired antioxidant status at the systemic level has been described in different chronic liver diseases and negatively influences graft function after liver transplantation (Poli G. 2000, Loguercio C 2003). 7-Ketocholesterol and 7beta-hydroxycholesterol, prototype molecules of free radical-mediated cholesterol oxidation, are very important oxysterols currently accepted as in vivo reliable markers of oxidative stress. High oxysterols plasma levels are associated with an alteration of normal plasma fatty acid pattern in cystic fibrosis (Iuliano 2009). The Model for End-Stage Liver Disease (MELD) score is a common score used routinely to stage liver function in patients with liver cirrhosis (Al Sibae 2010). After ischemia-reperfusion injury at liver transplantation oxidative stress, hepatic endoplasmic reticulum (ER) stress and cholesterol metabolism are interrelated key processes to preserve graft regeneration and function. A blood sample is obtained in each subject to measure MELD score at the first visit and at liver transplantation. Further blood samples are collected at days seven and 30 post transplantation. Blood samples are also obtained from healthy subjects. Liver biopsy samples are obtained from liver transplant donors. Oxidative stress and fatty acids lipidomics are measured to evaluate the actual plasma concentration in liver cirrhosis patients to be compared with healthy controls. Oxidative stress and fatty acids are also analyzed as a function of disease status, and for its influence on transplant outcomes. Lipid metabolism gene and endoplasmic stress reticulum gene expression are evaluated in liver biopsy specimen to study the influence on graft function.

Observational
Observational Model: Case Control
Time Perspective: Prospective
Not Provided
Retention:   Samples With DNA
Description:

Blood samples and liver biopsy specimens

Non-Probability Sample
  1. 150 cirrhotic patients, including Hepatocellular Carcinoma (HCC), Hepatitis C Virus (HCV) positive patients
  2. 80 healthy controls
  3. 100 liver donors
Liver Cirrhosis
Not Provided
  • Liver Cirrhosis
    Patient with liver cirrhosis undergoing liver transplant
  • Liver donors
    Subjects eligible for organ explant
  • Healthy controls

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
320
September 2014
July 2014   (final data collection date for primary outcome measure)

Liver cirrhosis inclusion criteria:

  • subjects with liver cirrhosis eligible for liver transplant, and one MELD score determination performed at least 3 months before liver transplantation

Liver cirrhosis exclusion criteria:

  • liver transplant contraindication and re-transplantation
  • current use of antioxidants and fatty acids supplements

Healthy controls are recruited recruited among the University personnel, after a review of their medical history.

Exclusion criteria for control participants included the use of drugs that affect fatty acids (systemic corticosteroids, isotretinoin, and ursodiol) and/or oxidative stress (antioxidants and hypolipemic drugs).

Both
15 Years to 69 Years
Yes
Contact: Stefano Corradini, M.D., Ph.D. +390649972086 stefano.corradini@uniroma1.it
Italy
 
NCT01389115
Iul_LC
Yes
Luigi Iuliano, University of Roma La Sapienza
University of Roma La Sapienza
Not Provided
Principal Investigator: Stefano Corradini, M.D., Ph.D. Sapienza University of Rome
University of Roma La Sapienza
January 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP